Immupharma Share Discussion Threads

[a_2_b] 20/5/2018 17:29

Lol don't give him some new fantasy to work off. He'll probably take credit for developing the disease on his secret island.

[badger60] 20/5/2018 16:02

I'm with you Nobby....... perhaps the reason not to bin Lupuzor now is ensure that the £10mio left in the bank is "spent wisely" by the management....;+)

[nobbygnome] 20/5/2018 15:28

Not with a p value of 0.28....

[kmjs] 20/5/2018 15:24

Thankyou.

We await expanded PhIII data from IMM, but if I were a Lupus sufferer on this
extended trial thinking the drug was helping me, I would be seriously angry if
someone decided to stop treating me, at least before full data has been analysed.

Many patient groups seem pretty ferocious in support of their need for new
treatments to these awful ailments and I get the sense with the new FDA head we
may see a far more lax route to approval than you have been used to in the past,
especially where a potential new drug shows little or no adverse reaction in
early trials.

[divinessence] 20/5/2018 15:11

immy1992 - a very good post and if data analysis proves the Mauritius patients skewed the results then game on though IMM have been a touch naive (or perhaps over confident) on statistical aspect of the results. However a further trial/analysis could easily correct this but this makes an intriguing takeover target for a Pharma, hence I am very positive on the next RNS. They are taking their time on it as it will be significant.

Agree entirely, the "clinical significance has been achieved in P2 & P3" and the drug WORKS.

Thank you for your post ...

20 May '18 - 11:14 - 31351 of 31362

I think the key difference from the p2 and p3 trial with regards to placebo effect was that p3 included 40 patients from one site in Mauritius .

In the p2 all patients were scattered across Europe with no one site having a significantly higher number of patients then the other.

In p3 all the European sites had 4-7 patients. Then they went and took 40 patients from just one site in Mauritius. A fact I overlooked. That's 20 percent of data points from a single trial centre. One could argue that this caused the placebo effect to be higher as it is fair to assume patients were in contact with each other. It is also fair to assume many of these patients from a less developed country like Mauritius may never have been given appropriate SOC or any SOC before which caused them to respond. Of course this is yet to be determined as full data has yet to be published, it's my speculation.

Efficacy in the p140 arm remained roughly the same as week24 results in p2. Also reading the p2 report again they powered p2 based on 20 percent placebo and 45 percent lupuzor. A huge mistake. They made that same powering mistake in the p3 trial i suspect.As you said the remission is a very intriguing and positive point.

Also as you know p3 was 52 weeks vs p2 24weeks. It could be suggested that over the course of 52 weeks full remission could be achieved with 90percent guarantee in 7 percent of patients.

Regarding statistics I'll just reiterate that it is just maths. You can prove 1 percent statistical significance as long as you power your trial adequately. Clinical significance has been achieved in p2 and p3 , however it was not statically significant due to powering and trial issues I believe.

[nobbygnome] 20/5/2018 15:01

So just to develop this point a bit, my position meant I had an advantage in terms of getting good information. For example I was in Uppsala in October last year with our excellent MSL in Sweden. She happened to have worked with a Lupus KOL who had his office there. So we popped in to have a general chat because he was an important guy for us and during the conversation I asked his opinion about Lupuzor. He had no idea why I was asking but unprompted said that the dosing level was 'too good to be true'. So I wasn't the only one to have grave concerns about the amount of drug which was being given. He went on to correctly predict that the phase III would be negative. I don't know for sure but he may well have been involved in some of the advisory boards for Lupuzor.

[nobbygnome] 20/5/2018 14:52

>> kmjs

For my main project I was the scientific lead and either the first or last author on more than 20 publications. When I say I was a bench scientist that was for the first 14 years or so and then I became the scientific lead as the drug went through development, approval and launch.

In industry you are expected to work on multiple projects but it would be surprising if I had also been lead on the Lupus drug. However, I was intimately involved as a secondary scientific expert on that project partly because of my experience on my main drug. So again I was with it all through it's clinical development.

I would just like to add that I also regularly reviewed papers in this field. This is extremely unusual for an industry scientist but I had very good scientific relationships with many KOLs in the rheumatology field, which meant they trusted my judgement to be able to review papers objectively. Of course many KOLs in RA are also KOLs in Lupus...

[kmjs] 20/5/2018 14:44

Thankyou

"However, I also worked on a drug in Lupus which spectacularly failed in phase III after apparently good 'cherry picked' phase II results".

Does your Lupus experience predate your work from the 90s to retirement?

When you say "I also worked on a drug in Lupus" was that as a "cog" or lead? I hope
that is not a bizarre question, as again I'm merely trying to guage your level of
experience/expertise in the field of Lupus.

When you say "as a bench scientist" is that generally a member of a team, or would a
"bench scientist" also be lead author?

Obviously, as I don't know your name I can't just "google" you.

[nobbygnome] 20/5/2018 14:36

>> kmjs

Sorry just read your original post again.

Why would posting here be unethical? Strangely I know more about this field than anyone else on this thread so it seems to make sense to share my experience....even if a lot of people don't want to listen. I am now essentially free of any confidentiality constraints, although the fact that I am probably going to get a consultantcy agreement with my previous company, means I can't give any more details about the product I worked on for 24 years in total.

[nobbygnome] 20/5/2018 14:13

>> kmjs

No I am not going to name the drug (for confidentiality reasons) but it is in different indications from Lupuzor but obviously similar rheumatology indications as well as gasterenterology. However, I also worked on a drug in Lupus which spectacularly failed in phase III after apparently good 'cherry picked' phase II results. Sound familiar....

In fact the p value was very similar to Lupuzor. Strangely my company decided it was absolutely pointless to continue development any further! There was even good data to support it's use in another indication but they took the prudent decision it wasn't worth risking £50 million plus on another trial. This is all so relevant don't you think...

Nobby

[kmjs] 20/5/2018 14:09

Thankyou for answering 2 of the 3 questions.

"My major achievement was over the last 14 years being the scientific expert for a particular drug which is now turning over £1 billion a year"

Would you say the drug you worked on is a competitor to Lupuzor if it were ever to
come to market? Is there a reason you don't seem to want to name the drug you worked
on for so long? It seems a little bizarre, surely that information is now
somewhere in the public domain?

[nobbygnome] 20/5/2018 13:44

>> sibecks

Good stuff! Indeed without the warm weather I would have done below 45......in my dreams at least

[sibeks] 20/5/2018 13:30

I ran a 10k as well today Nobbygnome in 47:24 also over 50 but I can do better just too hot

[nobbygnome] 20/5/2018 13:21

>> kmjs

What a bizarre series of questions. So one's scientific life stops as soon as you leave work? Why on earth do you think that? I am using it now more than ever.

My major achievement was over the last 14 years being the scientific expert for a particular drug which is now turning over £1 billion a year and more importantly treating hundreds of thousands of patients. I was involved in making the drug in the 90s as a bench scientist and then followed it through on to the market through all stages of development, registration, launch and marketing. That is why I have experience of the whole drug discovery and marketing process, which is very rare. However, my main expertise is most definitely the science. For the last 14 years I have been travelling quite literally all over the world talking about the science in the related field and will continue to do so now for patient associations.

You did ask.....

Nobby

[kmjs] 20/5/2018 13:09

31330

"Anyway science is my life"

Why did you take early retirement then? Don't enthusiastic eminent World leading scientist's usually stay at their laboratory bench until they "drop"?

If you are an eminent World leading scientist, do you not think your postings here
are somewhat unprofessional, unethical?

After 34 years reaching status of eminent scientist within your field, what was your
greatest achievement in the advancement of human medicine?

[nobbygnome] 20/5/2018 12:36

>> immy

I agree with most of what you say. The decision to have so many patients in Mauritius was so naive and sums up the mistakes the inept management have made.

However, until you do a much larger trial which is a massive risk you just don't know what the current trial was telling you other than the drug didn't work under the conditions and number of patients tested. You can't just extrapolate up the numbers and expect exactly the same result. All the trails done so far have failed on the primary end points. That is the reality.

[immy1992] 20/5/2018 11:14

Dr biotech.

I think the key difference from the p2 and p3 trial with regards to placebo effect was that p3 included 40 patients from one site in Mauritius .

In the p2 all patients were scattered across Europe with no one site having a significantly higher number of patients then the other.

In p3 all the European sites had 4-7 patients. Then they went and took 40 patients from just one site in Mauritius. A fact I overlooked. That's 20 percent of data points from a single trial centre. One could argue that this caused the placebo effect to be higher as it is fair to assume patients were in contact with each other. It is also fair to assume many of these patients from a less developed country like Mauritius may never have been given appropriate SOC or any SOC before which caused them to respond. Of course this is yet to be determined as full data has yet to be published, it's my speculation.

Efficacy in the p140 arm remained roughly the same as week24 results in p2. Also reading the p2 report again they powered p2 based on 20 percent placebo and 45 percent lupuzor. A huge mistake. They made that same powering mistake in the p3 trial i suspect.As you said the remission is a very intriguing and positive point.

Also as you know p3 was 52 weeks vs p2 24weeks. It could be suggested that over the course of 52 weeks full remission could be achieved with 90percent guarantee in 7 percent of patients.

Regarding statistics I'll just reiterate that it is just maths. You can prove 1 percent statistical significance as long as you power your trial adequately. Clinical significance has been achieved in p2 and p3 , however it was not statically significant due to powering and trial issues I believe.

[nobbygnome] 20/5/2018 11:08

PS I did 45:30 in the 10k race and came 5th in the over 50s category..... not bad for an old git!

[nobbygnome] 20/5/2018 11:05

>> francis

Strange that, I am way up on my VAL trading..... I sold the vast majority on the recent rise at over 100% profit and am now buying them back slowly. A licensing deal is coming shortly on 401 IMHO....

Nobby

[nobbygnome] 20/5/2018 11:02

Talk about being obsessed...talk about someone else FFS.

EVG are a very good bet at the current price IMHO. A positive interim phase II result in breast cancer is about to be announced, again IMHO. A 20 % response rate at 6 months is the key number to beat.

[francisgalton] 20/5/2018 10:23

If I'd followed Nobby gnome's trading, I would have missed the rise from 40p to 190p at Immupharma and I would have lost more than half of that money on Valirx instead.

[hamila01] 20/5/2018 10:18

I pay very little attention to what Nobby says. He called a failed trial correctly, hasn't called a failed drug correctly and was both long and short on IMM before results.He has an ego which would have declared success whichever way the result had gone....